Tay-Sachs disease (TSD) is a rare inherited disorder that progressively destroys the brain and nervous system. The body progressively loses basic functions, leading to deafness, blindness, and paralysis. Individuals with TSD usually do not live beyond five years of age. Infection is a common cause of death in TSD patients.

TSD is caused by mutations in the HEXA gene. This gene contains instructions for making the hexosaminidase A enzyme, which plays an important role in maintaining the central nervous system. The central nervous system, which controls many of the bodily functions, is eventually destroyed by TSD. Because it affects the nervous system, TSD is classified as a neurological disease.

TSD is named after British ophthalmologist Warren Tay and American physician Bernard Sachs, who independently described the symptoms of what would later be known as infantile TSD. In 1881, Tay described eye defects, which are characteristic of TSD, in an infant with a progressive neurological disease. In 1887, Sachs presented his observations of a disease that was prevalent among German immigrants of Jewish heritage.

TSD is a recessive genetic condition, which means that the mutation must be inherited from both parents for the disease to occur. People who have inherited the mutation from only one parent do not have TSD, but are called "carriers" because they may pass the disease on to their children. Historically, certain populations (such as French Canadians and those of Ashkenazi Jewish descent) had a higher proportion of carriers and thus a higher incidence of TSD.

TSD was among the first genetic diseases for which genetic screening was available. The accuracy of the TSD screening test, combined with professional counseling, has significantly lowered the incidence of TSD among formerly high-risk populations. Presently, the rates of TSD in the Ashkenazi Jewish and French Canadian populations are similar to those of the general population.

Symptoms of Tay-Sachs disease (TSD) typically appear between three to six months of age. Though some infants may appear normal during the first few months, nerve damage may have started while still in the womb. Fatty acid buildup in nerve cells causes the central nervous system (CNS) to deteriorate progressively.

Physical functions worsen over time, and those with TSD may lose muscle tone and strength. Patients are generally listless and display slow growth. TSD patients may have difficulty swallowing and may become paralyzed.

Neurological functions also deteriorate, leading to deafness, blindness, and seizures. Due to vision problems, patients with TSD often make little eye contact with others and may be easily startled. Mental and social development is also delayed.

Patients with TSD often have "cherry-red" spots in their eyes, which is a sign of nerve damage. This abnormality can be detected during an eye examination and is a characteristic of TSD.

A very rare form of the disorder, called late-onset TSD, may not appear until the 20s or 30s. Patients with late-onset TSD often develop neurological disorders and may have difficulty walking. Common symptoms include personality changes, muscle weakness or twitching, slurred speech, impaired thinking, poor memory, difficulty with comprehension, short attention span, and difficulty distinguishing between what is real and unreal (psychosis).

Eye examination: Tay-Sachs disease (TSD) may be diagnosed during an eye exam, which may reveal the characteristic cherry-red spot in the center of the retina. This is the area in the back of the eye that contains the photoreceptors, which are nerve cells that sense images.

Enzyme assay: TSD may also be diagnosed by an enzyme assay test. Low levels of the hexA enzyme in the blood may indicate TSD. This test may also identify carriers of TSD, who have only one defective HEXA gene. Even though they may not display any symptoms of TSD, they may have lower levels of the hexA enzyme assay. TSD is one of the first recessive genetic diseases for which the carriers could be identified.

Because hormone levels may affect the accuracy of this test, pregnancy or the use of birth control pills may lead to inconclusive results.

DNA testing: A very precise way to diagnose TSD is to locate mutations in the HEXA gene. Because these DNA tests are expensive, the enzyme assay test is generally used to make a preliminary diagnosis, and DNA testing is done only to confirm enzyme assay findings. DNA testing may also identify carriers of one mutated HEXA gene. DNA testing is often recommended for those with historical risk factors, such as Ashkenazi Jewish or French Canadian ancestry, or those with known family histories of TSD.

Amniotic fluid (prenatal) genetic testing: TSD may be diagnosed with enzyme assays in a developing fetus using blood samples taken from the fetus. Diagnosis of TSD may also be performed on an unborn baby through amniocentesis, in which the amniotic fluid surrounding the unborn baby is sampled through a needle. Genetic tests may also be performed on blood or amniotic fluid. Because taking a blood sample may cause harm to an unborn baby, taking samples of amniotic fluid is generally preferred. It is important to note that any prenatal test carries a risk of miscarriage.

Chorionic villus sampling (CVS): Chorionic villus sampling (CVS) is another type of prenatal diagnosis that can detect genetic problems in a fetus. Samples are taken from the chorionic villus, or placental tissue. As with any prenatal test, this procedure carries a risk of miscarriage.

Pre-implantation genetic diagnosis (PGD): A new procedure called pre-implantation genetic diagnosis (PGD) may be performed on embryos produced by in vitro (artificial) fertilization. This test allows parents to implant and carry only the embryos that do not carry the mutated genes that cause TSD.

Even with treatment, patients with Tay-Sachs disease (TSD) rarely survive beyond five years of age. A common complication is infection, which may be caused by a number of different agents including bacteria and viruses.

Similar complications may occur for patients with juvenile- or adult-onset TSD, although the risk of complications varies depending on the speed and severity of the nerve damage.

The nerve damage caused by TSD may also lead to seizures, which may result in choking or physical injury.

There is currently no cure for Tay-Sachs disease (TSD). Treatment focuses on managing the symptoms, preventing complications, and making the patient as comfortable as possible.

Medication: A number of different medications may be prescribed to manage pain or seizures in TSD patients. The type and dosage of medication may depend on the severity and frequency of these symptoms.

Assisted breathing: TSD patients may have difficulties with breathing and may thus require assisted ventilation with ventilators.

Assisted feeding: Because TSD patients may develop difficulties with swallowing, they may require feeding assistance. Assisted feeding may involve a nasogastric (NG) tube, which delivers nutrients through the nose and esophagus into the stomach. Tubes may also be inserted through the abdomen. These percutaneous esophago-gastrostomy (PEG) tubes must be inserted surgically but provide a more permanent feeding solution than NG tubes.

Physical therapy: As the neurological and motor functions begin to deteriorate in TSD patients, they may receive physical therapy to help stimulate the nerves and the muscles. Physical therapy may help to maintain joint flexibility and may also slow the loss of muscle function.

Family support: Many resources are available for families affected by TSD. Healthcare providers may offer educational materials to help families understand the nature of the disease. Support groups may also help families cope with the difficulties in caring for TSD patients.

Investigational therapies: A number of therapies are currently being investigated for treating TSD.

One experimental treatment, enzyme replacement therapy (ERT), involves introducing functional hexA enzyme into the patient. However, delivering the enzyme into cells remains a major hurdle in this type of therapy.

Substrate reduction therapy (SRT) involves reducing the production or amount of GM2 ganglioside. GM2 gangliosides may be processed with the enzyme sialidase (or neuraminidase), which can process lipids as well as proteins. Current challenges to this therapy revolve around increasing sialidase production in the nerve cells, where it would be needed to slow nerve damage in TSD. The drug OGT 918 (miglustat or Zavesca®) is being investigated as one type of SRT for treating late-onset TSD (LOTS). This drug, currently in clinical trials, reduces the production of GM2 gangliosides.

Gene therapy involves introducing functional copies of the HEXA gene into TSD patients. Various gene delivery methods have been investigated, including viruses or directly introducing DNA into cells. The safety and effectiveness of gene therapy has not yet been established and this therapy remains experimental.

Note: Currently, there is not enough evidence available on the safety and effectiveness of integrative therapies for preventing or treating Tay-Sachs disease (TSD). Seizure is a common complication of TSD that may have serious consequences. The integrative therapies for seizures listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies or preventive measures.

Good scientific evidence:

Yoga: Several human studies report a reduction in the number of monthly seizures with the use of Sahaja yoga when it is added to standard anti-seizure drug treatment or a yoga meditation protocol. This research is preliminary, and better studies are necessary before a firm conclusion can be drawn.

Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Certain yoga breathing techniques should be avoided in people with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction (the popular Lamaze techniques are based on yogic breathing). However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

Use extra caution during cervical adjustments. Use cautiously with acute arthritis, conditions that cause decreased bone mineralization, brittle bone disease, bone softening conditions, bleeding disorders, or migraines. Use cautiously with the risk of tumors or cancers. Avoid with symptoms of vertebrobasilar vascular insufficiency, aneurysms, unstable spondylolisthesis, or arthritis. Avoid with agents that increase the risk of bleeding. Avoid in areas of para-spinal tissue after surgery. Avoid if pregnant or breastfeeding due to a lack of scientific data.

Melatonin: The role of melatonin in seizure disorders is controversial. Better evidence is needed in this area before a clear conclusion can be drawn regarding the safety or effectiveness of melatonin in seizure disorders in children.

Based on available studies and clinical use, melatonin is generally regarded as safe in recommended doses for short-term use. Commonly reported adverse effects include fatigue, dizziness, headache, irritability, and sleepiness, although these effects may occur due to jet-lag and not to melatonin itself. Melatonin supplementation should be avoided in women who are pregnant or attempting to become pregnant, based on possible hormonal effects. High levels of melatonin during pregnancy may increase the risk of developmental disorders.

Vitamin E: Vitamin E has been evaluated as an addition to other drugs used to prevent seizures, particularly in refractory epilepsy. This evidence is not conclusive enough to make a clear recommendation. The management of seizure disorders should be made under medical supervision.

Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid above the recommended daily level in pregnant women and breastfeeding women.

Because Tay-Sachs disease (TSD) is an inherited genetic condition that progressively destroys the central nervous system (CNS), there is no known way to prevent this disease. However, genetic screening and counseling may reduce the risks of having children with TSD.

Couples may work with genetic counselors to evaluate the probability of having children with TSD based on known risk factors. Counselors may also help prospective parents decide the testing methods that are appropriate.

Carrier screening is possible through a relatively inexpensive and widely available enzyme test. Individuals with positive or inconclusive results with the enzyme assay test may undergo DNA testing, which is highly accurate but more expensive.

TSD was among the first genetic diseases for which genetic screening was available. The accuracy of the TSD screening test, combined with professional counseling, has significantly lowered the incidence of TSD among formerly high-risk populations. Currently, the main risk factor for TSD is a family history of the disease, regardless of ancestry.

Tay-Sachs disease (TSD) occurs when a child inherits one mutated HEXA gene from each parent. Normally, this gene contains the instructions for an enzyme called beta-hexosaminidase (hexA). This enzyme serves to break down a lipid (or fat) called GMT2 ganglioside. When the HEXA gene is mutated, this lipid accumulates in the brain and other tissues of patients with TSD. This leads to the deterioration of the brain and central nervous system (CNS).

The hexA enzyme is found in the lysosomes, which are compartments in the cell that are responsible for breaking down and disposing of waste material. Normally, the hexA enzyme serves to break down a substance called GM2 ganglioside, which is a lipid that is constantly made and broken down during nervous system development.

Mutations in the HEXA gene cause deficiencies in hexA enzyme activity, which allows GM2 ganglioside to build up in the cells and tissues of the CNS. Thus, TSD is classified as a lysosomal storage disorder. The accumulation of GM2 ganglioside is also known as GM2-gangliosidosis, which is a generic name for lysosomal storage disorders involving this lipid. If the buildup of GM2 ganglioside reaches toxic levels, it can destroy the nerve cells in the brain and spinal cord. This nerve cell damage is what causes the neurological symptoms of TSD.

Tay-Sachs disease (TSD) is extremely rare. TSD is a recessive genetic condition, which means that the mutation must be inherited from both parents for the disease to manifest. People who have inherited the mutation from only one parent do not have TSD, but are called "carriers" because they may pass the disease to their children. If one parent is a carrier, then each child has a 50% chance of inheriting one mutation and also of being a carrier of TSD. If both parents are carriers, each child has a 50% chance of inheriting one mutation. The chance of inheriting no mutations is 25%, and the chance of inheriting two mutations is 25%.

Worldwide, it is estimated that the carrier frequency of the HEXA mutation is one in 300. Although anyone can have these mutations, TSD may be more common in certain populations. Historically, mutations in the HEXA gene were very common among those of Ashkenazi Jewish descent. Prior to 1970, it was estimated that 1 in 30 Ashkenazi Jewish individuals carried one mutated HEXA gene, and 50-70 infants with TSD were born each year to Ashkenazi Jewish families.

Other populations may also have an increased risk for TSD. Prior to the introduction of genetic screening, French Canadian or Cajun populations had carrier frequencies similar to Ashkenazi Jewish populations (about 1 in 30).

The availability of genetic screening and counseling has significantly decreased the carrier frequency in populations that historically had high incidences of TSD.

Tay-Sachs disease (TSD) is classified into various forms based on when the symptoms first appear.

Infantile TSD (or early-onset TSD): The vast majority of TSD occurs early in life. Though nerve damage may begin before birth, the symptoms generally develop when the infant is three to six months old. The symptoms progress very quickly in infantile TSD, and patients rarely survive beyond five years of age.

Children with early-onset TSD may make very little eye contact with others. Other eye problems are common, including twitchy eyes and difficulty focusing on objects.

As symptoms progress, they may include limp and floppy muscles, decreased alertness, decreased playfulness, difficulty sitting up, poor motor skills, decreased hearing, gradual loss of vision, and an abnormally large head (macrocephaly). During the last stage of the disease, the child typically becomes blind, deaf, mentally impaired, paralyzed, and unresponsive. The patient may have difficulty swallowing or breathing and may have seizures.

Juvenile onset TSD: The symptoms of TSD sometimes develop during childhood. These patients typically die between the ages of 10 and 15.

Symptoms of juvenile-onset TSD are generally similar to early-onset TSD. However, symptoms of juvenile-onset TSD do not develop until the patient is between three and 10 years of age.

Late-onset TSD (LOTS) or adult-onset TSD: In extremely rare cases, TSD may not develop until the patient is an adolescent or adult. Although the nerve damage continues throughout life, the damage may progress relatively slowly and symptoms may be mild. Those with late-onset TSD may have normal life expectancies.

Symptoms of late-onset TSD may develop when the patient is an adolescent or in his/her mid 30s and may be milder than other forms of TSD.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.